SPUR 2021: VASCULAR CERAMIDE BIOSYNTHESIS DISRUPTS ENDOTHELIAL CELL BARRIER FUNCTION AND CONTRIBUTES TO COGNITIVE IMPAIRMENT IN MICE WITH AND WITHOUT ISCHEMIC STROKE, DEFINING THE CONTRIBUTION FROM ENDOTHELIAL CELL AUTOPHAGY AND PKC ACTIVATION TO VASCULAR COGNITIVE IMPAIRMENT, CHARACTERIZING METABOLISM IN ENDOTHELIAL CELLS OBTAINED FROM HEALTHY INDIVIDUALS AND PATIENTS WITH CARDIOVASCULAR DISEASE

Faculty Name:
J David Symons

Department:
Nutrition & Integrative Physiology

Faculty College:
Health

Email:


Project Description:

**This project is a part of the Summer Program for Undergraduate Research (SPUR), which provides undergraduate students with an intensive 10-week research experience under the mentorship of a University of Utah faculty member. SPUR 2021 begins on May 26 and ends on August 5. If you are interested in this project, please review all program information on the SPUR site. If you wish to apply to this project, you must apply using the SPUR 2021 application.**

Project 1. Vascular dysfunction contributes to cognitive decline. Our lab has shown that ceramide accrual in preclinical models of type 2 diabetes (T2D) leads to vascular dysfunction. It is unknown whether vascular ceramide biosynthesis leads to cognitive decline in preclinical models of T2D and / or exacerbates cognitive decline in preclinical models of T2D upon exposure to ischemic stroke. We will use novel, vascular specific, “gain of ceramide” and “loss of ceramide” murine models to explore this.

Project 2. Cardiovascular diseases affect 80% of persons > 65. Cognitive decline is associated with an aging endothelial cell phenotype, but the mechanisms are unknown. Repressed endothelial cell autophagy mimics an aging phenotype and we will determine whether this is sufficient to evoke cognitive decline in young mice. Importantly, we will assess the potential for a novel small molecule – bryostatin – to correct EC homeostasis to an extent that maintains cognitive function in older mice.

Project 3. We obtain endothelial cells (ECs) that line the arteries of healthy individuals and patients with cardiovascular disease. After verifying the purity of the ECs, we treat them with a variety of agonists and antagonists to evaluate their integrity. Next, we use unbiased discovery approaches to discern signaling pathways that might be upregulated or downregulated in the context of aging, hypertension, diabetes, heart failure.



Opportunity Type:

This is a paid research position


Student Role:

Students play an extremely important role in every experiment. Past student involvement has included: experimental set-up; assessing arterial function; quantifying intravascular signaling pathways; metabolic phenotyping; sectioning and staining brain tissue for infarction, neuroinflammation, neurodegeneration, ceramide accrual; animal husbandry; cognitive assessment of mice; data collection, reduction, analysis, interpretation, and presentation; flow cytometry; qRT PCR, western blotting; and evaluating subject and patient records. Remote Contingency Plan: Remote undergraduate research internship contingency plans have been in effect since March 2020. Examples include : 1) vascular data reduction, entry, analysis, and statistical evaluation; 2) histology imaging, analysis. and evaluation; 3) subject and patient record interrogation and organization. All students attend lab meetings and seminars via zoom when their schedule permits, and one-on-one meetings with the PI when their schedule permits. Another potential scenario is restricted laboratory access vs. completely remote. We have implemented this successfully as well. Students come to lab on pre arranged schedules, to facilitate physical distancing and minimize laboratory density. Students have been trained and completed experiments in this mannerl.


Student Benefits:

Learning outcomes. Students will learn: the daily routines of an academic researcher, MS student, PhD student, Postdoctoral Scholar, and Junior faculty member; cardiovascular physiology in general, and vascular biology in particular; the scientific method; various laboratory tests / procedures; how to critically evaluate data that are being collected; organization and time management skills; how to make an effective data presentation in oral and / or poster format. Benefits. If you choose to go on to one of the pre-health professions, and your interviewer asks "tell me about your research" ... you will be able provide a succinct answer that includes: the background/rationale/clinical relevance of your topic; your directional hypothesis(es); methods you used; main results you obtained; how your findings synthesize with what is known currently; and how you moved the field forward in a manner that was NOT incremental. Furthermore, it is hoped that you will be able to tell them that you presented your findings at a local, national, and / or international conference. We will help you to accomplish this.


Project Duration:

35-40 hours per week on research and program-related activities, begins May 26, 2021, and ends August 5, 2021


Minimum Requirements:

Admission to the program is competitive. Applicants must meet all of the following criteria: 1) be a matriculated, degree-seeking undergraduate student in the Fall 2021 semester (beginning or continuing college career in Fall 2021 and not graduating before December 2021; concurrent enrollment while in high school does not meet this eligibility requirement). Applicants do not need to be a University of Utah student. 2) eligible to work in the United States: If you are a University of Utah Dreamer (with or without DACA), you are eligible to participate. If you are a Dreamer from a different institution: If you have DACA, you are eligible to participate. If you do not have DACA, you are able to participate and gain research experience, but might not be able to be compensated. For more information, please contact Megan Shannahan at megan.shannahan@utah.edu or 801-581-2478. If you are an international student or scholar, you must either a) be a degree-seeking undergraduate student at an American institution of higher education and verify with your institution’s international center that your visa allows you to participate in this program, OR b) possess documentation that establishes your eligibility to work in the United States (if you hold US citizenship, it is likely you have these documents). 3) able to commit to approximately 35-40 hours per week of employment at the University of Utah for the entire duration of the program (May 26-August 5, 2021). 4) at least 18 years old by May 24, 2021 (required if you wish to use on-campus housing; preferred if you will not be using on-campus housing). Please note that no previous college coursework or previous research experience is required.